Antibodies injected into a small number of Alzheimer's Disease (AD) patients appear to have stopped the progression of Alzheimer's by attacking the plaques assocated with the disease.
Immunoglobulins which are already being used to treat multiple sclerosis may also be able to help patients with Alzheimer's. This, at least, is the finding of a pilot study on five patients at the University of Bonn. The results are set out in the forthcoming edition of the Journal of Neurology, Neurosurgery and Psychiatry (vol. 75, pp. 1472-1474), which also devotes its editorial to this discovery.
Immunoglobulins contain, among other things, anti-bodies against a protein which is the 'main suspect' thought to trigger off Alzheimer's. After six months of immuno-globulin doses the concentration of this protein in the patients' cerebrospinal fluid was reduced by one third. The patients' cognitive abilities improved slightly.
Even if the treatment is effective it is not surprising there was not a bigger improvement in cognitive function. AD kills neurons. A halt of the disease progression is still going to leave current AD patients with a lot of brain damage. Even if replacement neurons can eventually be grown a large portion of who an AD sufferer was originally is irretrievably lost.
However, the medical team involved emphasise that their findings are still very tentative. They are now planning a large-scale double-blind clinical trial with about sixty patients so as to further confirm the positive effect of the immunoglobulins.
The cerebral cortex of Alzheimer's patients regularly contains large protein aggregates, what are known as Alzheimer's glands. They predominantly consist of beta-amyloid peptide, a small protein. This peptide collects in the brain of Alzheimer's patients and forms protein deposits which can damage and even destroy the sensitive nerve cells.
A promising approach in combating the disease seems to be the treatment with anti-bodies which are specifically effective against beta-amyloid. Thus, in animal experiments the injection of beta-amyloid anti-bodies led to a reduction in the protein deposits and an improvement in the behavioural deficits in these animals. Another study recently showed that immunising was not only able to reduce amyloid plaques, it also prevented the formation of the abnormal tau protein.
Recently the team led by the Bonn lecturer Dr. Richard Dodel was able to show that every person's blood contains anti-bodies against beta-amyloid, but that the concentration in Alzheimer's patients is markedly lower. Their findings have been confirmed by two US teams. 'There are already anti-body blood preparations which are used for particular diseases of the nervous system such as multiple sclerosis, which are known as immunoglobulins,' Dr. Dodel explains. 'We have now investigated whether these preparations contain anti-bodies against beta-amyloid and if these can be used to fight Alzheimer's.' His team did in fact find anti-bodies in one type of immunoglobulin medication which are very effective specifically against beta-amyloid. In a pilot study carried out on five Alzheimer's patients the team then studied the effect of the immunoglobulins on the progress of the disease. This involved giving the patients an immunoglobulin injection intravenously every four weeks throughout the six-month study. Before beginning and on completing the therapy the researchers determined the beta-amyloid content in the blood and the CSF fluid – the latter being the liquid which is present in the brain and spinal cord. 'On average the beta-amyloid concentration in the fluid decreased in the course of the study by over 30 per cent, while the concentration in the blood rose 2.3 times,' Dr. Dodel says. 'The immunoglobulins therefore seem to have the effect of flushing out the beta-amyloid from the brain' – how exactly this occurs is as yet unclear.
At the same time the team carried out various tests which enabled them to check the cerebral performance of dementia patients. After six months four of the five patients did slightly better than before in what is known as the ADAS-cog test (Alzheimer's Disease Assessment Scale, cognitive subscale). In the MMSE (Mini-Mental State Examination) test three patients improved. 'What is even more remarkable is that none of our test persons deteriorated,' Dr. Dodel explains. 'Without treatment Alzheimer's patients on average score seven to eleven points worse in the ADAS-cog test one year later, and even patients on medication score four to six points worse. In our study they improved on average by 3.7 points.'
These researchers still need to follow up with a larger and double-blind study that they are planning. But if ths treatment could work it would save the minds of tens of millions of people (4.5 million Americans currently suffer from AD) while saving the families of those sufferers enormous amounts of work, money, and a tremendous stress and burden.
This result is not surprising. In a previous study with a vaccine called AN-1792 many of the patients experienced a slowing or stopping of Alzheimer's Disease progression. Unfortunately, 17 out of the 300 patients in that study developed an encephalitis probably caused by an auto-immune response. But if I was an Alzheimer's Disease patient who was just diagnosed (i.e. if I still could reason well enough to make choices) I'd jump at those odds and take the risk of the encephalitis. However, governments do not let us take risks even when we are in the process of losing our minds to a fatal disease.
Another Alzheimer's vaccine appears to work in rhesus monkeys. Also, drugs are under development to block beta amyloid plaque formation.
With the baby-boom generation aging and life expectancy continuing to increase, Alzheimer's disease has become a ticking time bomb. The fastest-growing segment of the population is 85 and older. In Mr. Dillon's age group, 65 to 74, 3 percent have Alzheimer's; in the 85-and-over group, it is a staggering 47 percent, according to the National Institutes of Health.
Absent an effective treatment the number of AD cases is expected to triple by the middle of the 21st century. However, AD is a much more approachable problem as compared to cancer. The proteins that form into plaques that appear to play a vital role in AD development are turning out to be removable via immune system approaches. So I expect that within 20 or 30 years we will have effective treatments to stop AD progress. However, once we can stop the disease that will still leave millions with the brain damaged they suffered before a cure was developed. Also, while effective treatments are probably going to happen in the next couple of decades this is not reason for complacency. We ought to be trying even harder to achieve a cure. Money spent on AD research will pay itself back many times over.
If you want to reduce your risk of AD then my advice is to get lots of omega 3 fatty acids to slow disease progess and plenty of folic acid and vitamin B12 to keep down blood homocysteine which is an AD risk factor. If you are curious to review the literature on AD risk factors check out this list of summaries of AD risk factor studies. Even if some of the controllable factors listed there do not help reduce the risk of AD a diet aimed at those factors will certainly lower the risk of heart disease and stroke. Exercise helps lower Alzheimer's Disease risk too.
|Share |||Randall Parker, 2004 September 21 03:37 PM Brain Alzheimers Disease|